Dr. Peter Como presented to the U.S. Food and Drug Administration Neurological Devices Panel examining the reclassification of electroconvulsive therapy (ECT) devices on January 27, 2011. This presentation comes from the public record of the meeting.
The FDA systematic review of the literature of cognitive adverse events [of ECT] included only randomized controlled trials as I mentioned. However, we did examine data from crossover designs if analyzable pre-crossover data were available. In addition, studies had to use standard psychometrically validated neuropsychologic tests.
The statistical comparisons that were examined included comparisons among various ECT treatment conditions, such as electrode placement, energy dose, frequency of treatment, waveform, and pulse. The comparisons also included ECT versus sham, ECT versus other treatments such as drug and medication placebo, and comparison of pre- and post-ECT changes in baseline cognitive test performance, although the pre- to post- ECT comparisons in themselves were non-randomized.
From this literature search, a total of 68 studies were identified which met these criteria.
This slide summarizes the findings of the published systematic reviews, meta-analyses, and practice guidelines. Overall, these sources indicate that there is evidence for impairment in orientation, anterograde and retrograde memory, and global cognitive function immediately after ECT that may last up to six months. Autobiographical memory is the most commonly reported memory impairment in these reviews. There is limited evidence to suggest that the effects of ECT on memory and cognitive function may not last more than six months.
A greater risk of memory or cognitive impairment is associated with sine wave compared to brief pulse ECT, bilateral and dominant hemisphere electrode placement, and the use of high energy dose ECT. This literature also suggests that raising the electrical stimulus above the individual seizure threshold increases the efficacy of ECT but at the expense of greater memory and cognitive impairment.
To continue, these summaries report that patient self- reported memory loss tends to be more persistent than the deficits that can be measured on formal neuropsychological testing. However, for those patients who do experience memory or cognitive impairment, they consider this to be a considerable source of distress for themselves and their families. The effects of ECT on cognitive function do not appear to differ among various psychiatric diagnoses such as schizophrenia and mania.
These summaries also suggest that factors other than the ECT treatment may impact cognitive function. These include individual variability, degree of improvement in depression, and the use of psychotropic medications at the same time as ECT.
I will not present the findings from the FDA systematic review of the cognitive adverse events literature. As noted earlier, FDA identified 68 studies which met the search criteria.
Cognitive Abilities Impacted by ECT
The specific cognitive domains for which data was available are listed on the next two slides. Bear in mind that the classification of cognitive domains is not mutually exclusive as there is considerable overlap among various cognitive functions.
Orientation includes person, place, and time, is most often measured by the number of seconds to minutes needed for a patient to become reoriented following ECT. Executive function includes aspects of attention, mental tracking and planning, problem solving, response inhibition, set-shifting, and working memory. Global cognitive function is typically a composite score on tasks of multiple cognitive domains. In the ECT literature, the most commonly used measure is the Mini Mental State Examination. Global memory typically is a composite score on a standardized memory battery. The most commonly used measure in the ECT literature is the Wechsler Memory Scale, although there are numerous other batteries that have been studied.
Anterograde memory, also commonly referred to as short- term memory, is the capacity to encode, store, and retrieve novel verbal and non-verbal information. Retrograde memory, also commonly referred to as long-term memory, is the capacity to retrieve information encoded prior to the initiation of ECT and is typically reported in the literature as personal or autobiographical memory, which is the ability to recall past personal information and events, such as birthdays, anniversaries, et cetera. Impersonal retrograde memory is the ability to recall historical or factual information such as the colors of the American flag or past presidents. Subjective memory is typically a patient’s self-report scale of perceived memory problems.
Other cognitive abilities, including language, visual, spatial, and motor function, among others, are typically part of a formal neuropsychological test battery. However, there are relatively few studies in the ECT literature examining these cognitive functions and therefore are not included in this presentation.
In reviewing the cognitive adverse events literature, there is a lack of consistent methodology regarding the time points of when cognitive assessment takes place. In reviewing the literature, the cognitive assessment time points generally fell into these categories. Acute effects are those occurring within the first 24 hours of ECT seizure termination. Subacute effects are those occurring from 24 hours to less than 2 weeks. Medium-term effects are those occurring from 2 weeks to less than 3 months. Longer-term effects are those occurring from 3 months to less than 6 months, and long-term effects are those occurring at 6 or more months.
There’s also some lack of consistency in the literature with respect to energy dose utilized. The FDA review of the cognitive adverse events literature generally categorized energy dose as follows. Low dose is considered to be 1 to 1.5 times the seizure threshold, moderate dose is 1.5 to 3 times the seizure threshold, and high dose is defined as more than 3 times the seizure threshold.
The cognitive and memory adverse events literature also looked at the effects of electrode placement. Electrode placement is generally categorized in the literature as bilateral, which for many studies consists of bitemporal placement, bifrontal placement, unilateral which consists of unilateral nondominant hemisphere and/or right unilateral hemisphere, and finally left unilateral or unilateral dominant hemisphere. All of these terms are in the literature.